Effect of NF-κB inhibitors on the chemotherapy-induced apoptosis of the colon cancer cell line HT-29.

This study aimed to investigate the impact of the combined use of the nuclear factor-κB (NF-κB) inhibitors pyrrolidine dithiocarbamate (PDTC), bortezomib or SN50, and the chemotherapy agents arsenic acid (As(2)O(3)), fluorouracil (5FU), oxaliplatin or paclitaxel on the growth and apoptosis of HT-29 cells. Cell morphology was observed using inverted microscopy, and cell viability and apoptosis were assessed using the MTT assay and flow cytometry, respectively. The activities of NF-κB were analyzed by western blotting and electrophoretic mobility shift assay (EMSA). Cell growth was significantly inhibited by As(2)O(3), oxaliplatin and paclitaxel in a time- and concentration-dependent manner (P<0.05), while 5FU inhibited cell growth in a time-dependent manner only (P<0.05). The growth inhibition rate and apoptosis induction ratio were increased following the combined treatment of the chemotherapy agent and NF-κB inhibitor. The expression of NF-κB p65 was upregulated when cells were treated with a chemotherapy drug, however it was downregulated following combined treatment or treatment with an NF-κB inhibitor alone. In conclusion, an NF-κB inhibitor combined with a chemotherapy drug effectively inhibited cell proliferation, induced cell apoptosis and inhibited NF-κB activity to enhance the chemotherapeutic sensitivity of HT-29 cells.

Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese.

OBJECTIVE: Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS: A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS: Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ(2) = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122-2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ(2) = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113-2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION: This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.